Hormone Replacement Therapy

Last updated date: 22-Nov-2023

Originally Written in English

Hormone Replacement Therapy

It is unavoidable for women to experience menopause at some point in their lives. Hot flashes, nocturnal sweats, vaginal dryness, diminished sex drive, hair loss, vaginal and bladder infections, and other symptoms will be experienced. While these symptoms will not affect all women, they will affect a large number of them. All of these symptoms are caused by the fact that women stop ovulating at a particular age. Although the ovaries normally have a large number of healthy eggs, they no longer produce estrogen, the female sex hormone that controls the menstrual cycle. Women are no longer capable of bearing children as a result of this.

Hormone replacement therapy is a method of treating women who have insufficient levels of one or more female hormones in their bodies. Estrogen and progestin, a synthetic version of progesterone, are the most regularly used hormones. Hormone replacement therapy is most commonly used to address women's most serious symptoms, which include mood changes, sleep difficulties, vaginal dryness, lower sexual desire, and excessive sweating.

Hormone replacement treatment has had a significant impact on the medical area and filled gaps in our healthcare, but the benefits and drawbacks of these advancements are yet unknown. Early trials revealed that hormone replacement therapy was not only important in alleviating the symptoms of menopause, but it also had the potential to reduce the risk of heart disease and osteoporosis-related bone fractures. Estrogen's role in the body is to raise the good cholesterol level in the blood while lowering bad cholesterol levels. High-density lipoprotein (HDL) is the good cholesterol, and low-density lipoprotein (LDL) is the bad cholesterol. As a result, estrogen, which is one of the primary components of hormone replacement therapy, would appear to be a useful component in the formulation of anti-menopausal medications. However, the negative implications of standard allopathic drugs far exceed the potential benefits in terms of providing enough alleviation from menopausal symptoms.


Menopause Symptoms

Menopause Symptoms

Menopause occurs when a woman's menstrual cycle stops, signifying the end of her reproductive potential. Menopause can occur at any age, although it is most common in women in their fourth or fifth decades of life when they are 51 years old. Menses may stop before this age due to certain medical or surgical problems. Menopause is identified early if it happens before the age of 40.

The American Society for Reproductive Medicine's STRAW classification reflects the normal transition in a woman's life from her reproductive years to menopause.

The reproductive years are split into three categories: early, peak, and late, with regular menstrual cycles. This is followed by the menopausal transition stage, which is marked by a fluctuating cycle period that differs from normal by more than 7 days. Women have amenorrhea intervals of more than 60 days during the latter stages of this transition period. This type of amenorrhea is categorized as post-menopause when it lasts for more than a year. Perimenopause is defined as the time between the start of the menopause transition and the end of the final menstrual period, which is one year after the last menstrual period.

Symptoms experienced by women throughout perimenopause and menopause vary widely in extent and severity. The effect of lower estrogen levels in the blood on numerous organ systems causes symptoms. The most prevalent symptom of menopause is hypothalamus-mediated vasomotor instability, which causes hot flashes, sweats, and palpitations. More than 60 percent of postmenopausal women have these symptoms.


Common Symptoms

The following are some of the most common menopausal symptoms:

  • Irregular menstrual cycles
  • Sweating
  • Hot flashes
  • Palpitations
  • Vaginal dryness
  • Soreness
  • Superficial dyspareunia
  • Urinary frequency and urgency
  • Mood changes
  • Insomnia
  • Depression
  • Anxiety
  • Effects on the vasomotor system


Vasomotor System Effects

The most prevalent initial symptom in postmenopausal women is vasomotor dysfunction. Its specific cause is unknown; however, it is thought to be mediated at the hypothalamic level. Estrogen regulates the amounts of neurotransmitters in the central nervous system, which helps with thermoregulation. Reduced levels of these transmitters may cause instability in their usual concentration during menopause, resulting in hot flashes, nocturnal sweats, and excessive sweating.


Urogenital System Effects

Estrogen is necessary for the urogenital systems' proper function to be maintained. Reduced serum concentrations of this hormone during menopause are linked to a shift in the urogenital organs' microenvironment. The mucosal lining of the urethra, urinary bladder, vaginal canal, and vulva thins and atrophies. Vaginal flexibility and elastic properties are lost, and the vagina becomes short and narrow. The vaginal glands' normal discharges are diminished. The underlying subcutaneous connective tissue and the subepithelial vessels also show degenerative changes over time.

The formation of epithelial-cell glycogen reduces as endogenous estrogen levels fall. This adjustment alters the vaginal and bladders' typical alkaline environment. The acidic pH that results changes the local flora of the genitalia and urinary bladder, enabling gram-negative bacteria and fungus to colonize them and exposing the woman to repeated urinary tract infections.


Bone Metabolism Effects

Bone Metabolism Effects

During childhood and teenage years, bone mass steadily rises until it reaches a plateau in the third decade of life. The peak bone mass of men is above that of women. As a result, age-related bone loss is influenced by a complex interaction of factors, including gender, family history, food, and activity. Women are more vulnerable than men, and menopauses' decreased estrogen levels can hasten gradual bone loss, especially in the first five years after menopause. Postmenopausal women are more likely to have osteoporosis and osteoporosis-related fractures as a result of this scenario. Fragility fractures, which generally occur in the femoral neck, vertebra, or distal forearm, have a 40% lifetime risk in a 50-year-old woman.


Cardiac Function Effects

Women's natural resistance to heart disease begins to wane as they approach menopause. By the age of 65, their chances of having a heart attack are on par with men's.  The drop in estrogens' positive effects on plasma blood lipids levels, insulin sensitivity, body fat distribution, blood clotting, fibrinolysis, and endothelial function is thought to be the cause of this greater susceptibility to heart disease.

In both men and women, serum fibrinogen and plasma activator inhibitor (PA1) levels are strong predictors of heart disease.  Menopause is linked to higher levels of fibrinogen and plasma activator inhibitor in the blood, according to research. All of the aforementioned variables lead to postmenopausal women's higher risk of morbidity and mortality.


Hormone Replacement Therapy Indications

Hormone Replacement Therapy Indications

Hormone therapy can be used for symptomatic or preventative purposes. Although there is some agreement on the use of hormone replacement to treat symptoms, the use of hormone replacement to prevent menopausal complications is debatable. Hormone replacement therapy is commonly utilized in the following clinical circumstances:

  1. Vasomotor symptoms: the most frequent symptoms of menopause, such as hot flashes, sweating, and palpitations, are relieved by hormone replacement therapy. In placebo-controlled randomized trials, the efficacy of this medication was demonstrated.
  2. Urogenital symptoms: vaginal dryness, superficial painful intercourse, and urinary frequency and urgency have all been proven to improve with topical and systemic estrogens. Long-term therapy is required to achieve these favorable benefits. When hormone replacement is stopped, symptoms frequently return.
  3. Osteoporosis: it affects one in every three postmenopausal women. Hormone replacement therapy is routinely recommended to patients to avoid this disease, and it looks to be especially helpful if initiated during the first five years of menopause. Hormone replacement is beneficial to women who have low bone mineral density and have a history of bone fractures. Hormone replacements' bone-protective properties are also beneficial to women who are approaching menopause prematurely. They may, however, lose their protection if they stop taking hormones. Depending on the outcomes of the WHI study, 5 years of combined hormone replacement therapy decreased the prevalence of hip fractures by about 1 case per 1000 women under the age of 70 and by about 8 instances per 1000 women aged 70 to 79.


Hormone Replacement Therapy Contraindications

Oral or transdermal estrogen-based therapy has the following contraindications:

  • Breast cancer (known, suspected, or previous)
  • Other estrogen-based cancers, such as uterine cancer (known or suspected). Hormone replacement therapy is still an option for women who have had a hysterectomy and have no signs of the disease.
  • Deep venous thrombosis (DVT) or pulmonary embolism that is active or has occurred in the past
  • Factor V Leiden mutation carriers are the most frequent type of blood clotting problem.
  • Active or previous thrombotic disorders of the arteries, such as myocardial infarction or stroke
  • Chronic hepatitis or liver dysfunction

Because the serum levels of estrogen from this route are exceedingly low, these contraindications are not applicable to transvaginal-based estrogen therapy. The North American Menopause Society has suggested that transvaginal estrogen therapies be exempt from the black-box warnings that apply to conventional hormone replacement therapy.


Route of Administration

Many estrogen and progestogen options are available, and they can be taken orally or trans-dermally through cream, patch, vaginal implants, or subdermal pellets. Each route of administration has its own set of advantages and disadvantages.

  1. Oral Estrogen: Oral estrogen causes a rise in activated protein-C resistance, which raises the risk of a blood clot. Oral estradiol also causes matrix metalloproteinase 9 to accumulate in the liver, which reduces the production and rupture of atherosclerotic plaque.
  2. Transdermal Estrogen: Eliminates the danger of blood clotting by bypassing the liver metabolism that causes activated protein-C resistance.

The majority of progestins are taken orally, while a few are available in patch version in combination with estrogen. For non-FDA-approved purposes, progesterone is offered in an oral form that can also be used vaginally.

Combined estrogen and progesterone creams, sublingual troches, and vaginal implants are available from specialized pharmacy, but they are not FDA authorized.


Which Type is Right for You?

Unless you have a medical need to take a certain kind of HRT, selecting how to take it may be a matter of personal choice. It's critical to talk to the doctor about your health information and the many types of HRT. The following are the key choices:


Oral Tablets

Oral Tablets

Tablets are one of the most convenient and widely used forms of HRT (either combination or estrogen-only). All you have to do is remember to take the medication once a day.

If you're interested, try it if you desire a simple and easy-to-take type of HRT, and you don't have a history of heart problems, strokes, or liver problems, as the tablet form can modestly raise your chance of these disorders, but the risk is quite minimal.


Skin Patches

Skin Patches

Skin patches are applied to the skin and replaced every several days. Patches with both estrogen and progesterone are available. 

If you have a history of clotting, diabetes, cardiac or liver problems, or if you favor this approach over tablets or gels, try it. This kind of estrogen has less danger than tablets. Patches are simple to apply: simply peel off the paper and put the patch to a hairless region of the body, such as the upper arm, hip, or upper thigh. It ensures that hormones are absorbed consistently and does not harm the liver or raise the risk of clotting.


Estrogen Gel

Estrogen gel is a common type of hormone therapy that you apply once a day to the skin with a pump-action container. The hormone therapy, like the patches, is absorbed through the skin.

If you're interested, try it if you don't want to have to replace the patches every two or three days, and you're concerned that patches would hurt the skin. If you have a history of heart issues, diabetes, or clotting, you may be able to use the gel instead of the pill because it is associated with fewer hazards. It's also simple to use.


Vaginal Estrogen

Estrogen is applied to the vaginal area in the form of a cream, pessary, or ring.

Try it if you wish to treat vaginal dryness and uncomfortable intercourse but don't have additional symptoms like hot flushes that this type of hormone therapy won't help with. This type of hormone therapy raises estrogen levels in specific areas of the body without affecting the entire body. This is an extremely safe drug with low side effects, and it can be used without a progestogen if you still have a uterus.


Estrogen-only Hormone Therapy

If you don't have a uterus, give it a shot. This is because, while the danger is modest, estrogen-only hormone therapy, when done without progesterone/progestogen, may modestly raise the risk of uterine or ovarian cancer. It's good for the heart, and younger women who take estrogen-only hormone therapy have a decreased risk of heart disease than those who don't.


Combined Hormone Therapy

Combined Hormone Therapy

If you're interested, try it because the progestogen defends against a very modest higher risk of uterine cancer related to estrogen-only hormone therapy. use it when you still have a uterus.

If you have menopausal symptoms but are still having periods, cyclical combined hormone therapy is the best option. This entails taking a break between progestogens doses for a length of time. If you're postmenopausal and haven't had a period in a year, you should take continuous combined hormone therapy. This entails taking estrogen and progestogen on a daily basis without missing a day, and it is thought to lower the risk of uterine cancer.



Hormone Replacement Therapy Complications

Hormone Replacement Therapy

Hormone therapy is associated with a number of minor side effects that normally go away on their own. To avoid treatment discontinuance, the patient should be informed.

The following are some of the possible side effects:

  • Nausea
  • Bloating
  • Weight gain (equivocal finding)
  • Fluid retention
  • Mood swings
  • Breakthrough bleeding
  • Breast tenderness

The world women’s initiative (WHI), the largest study of its type, was begun by the National Institutes of Health in 1991. About 160,900 healthy postmenopausal women aged 50-78 years participated in double-blind, randomized, controlled trials as part of this project. Three clinical trials were performed at the same American facilities to see if menopausal hormone therapy, dietary changes, and calcium and vitamin D supplements could help prevent heart disease, osteoporosis, and breast and colorectal cancer. A total of 10,000 women who had received a hysterectomy were enrolled in the trial, and they were given just estrogen. Around 16,000 women in the other arm were given a combination of estrogen and progestogen. The trial was supposed to last until 2005, but it was discontinued in early 2002 after researchers discovered an elevated risk of breast cancer and concluded that the hormones' overall hazards outweighed potential benefits throughout the three decades analyzed.

Breast cancer, stroke, and heart disease rates did not increase in the fifth decade, but grew in the sixth and seventh, according to a reanalysis of the WHI data by age cohort. The risk of breast cancer was evident in women who had been given hormone therapy before entering the WHI trial after a washout period, but not in women who had never been subjected to hormone therapy.


Hormone Therapy and Breast Cancer

Although trials have been contradictory, a growing body of evidence suggests that hormone therapy may elevate the risk of breast cancer by a small amount. This risk is identical to that of natural late menopause, and it occurs after at least 5 decades of sustained hormone therapy use. When current long-term hormone therapy is initiated in women 50 years or older, the lifetime chance of getting breast cancer increases considerably. Women who begin hormone therapy early for premature menopause do not experience this consequence. This finding suggests that the duration of lifetime sex hormone exposure is important.


Mammography Density

According to a randomized placebo-controlled trial, mammographic density increases in roughly 25 percent of women who take both types of hormone therapy. The percentage increase in density is 5%. Estrogen and tibolone have no impact when they are unopposed.

The Million Women Study's findings were in opposition to evidence from placebo-controlled trials, which showed that both unopposed and combination hormone therapy increased density. Other observational evidence suggests that stopping hormone therapy for a few weeks prior to mammography could increase the imaging sturdy's accuracy. 


Survival with breast cancer while receiving hormone therapy

It's impossible to know how long patients with breast cancer who receive hormone therapy live. Overall, observational data indicate that hormone therapy has no effect on survival when compared to no hormone therapy.

Obesity has a role in the relationship between hormone use and breast cancer. For slim women, hormone use raises their risk of breast cancer, but not for overweight women. After menopause, adipose tissue is the principal source of endogenous estrogen, and estrogen concentrations in the body are significantly higher in obese postmenopausal women. As a result, supplemental estrogen may have less impact on estrogen bioavailability in overweight women compared to thin ones.


Hormone Therapy and Endometrial Cancer

Zeil and Finle established a link between external estrogen administration and a higher likelihood of endometrial cancer. Data from randomized controlled research has lately revealed a clear link between hormone therapy and uterine hyperplasia and cancer. This observed risk is related to hormone therapy based on unopposed estrogen, as opposed to the high risk of breast cancer attributed to combination rather than unopposed hormone therapy.

Continuous combination regimens have not been linked to a higher risk of developing cancer.  Following 5 years of use, however, cyclical regimens—even those using 10-14 days of synthetic progesterone per month—do raise the risk.


Hormone Therapy and Thromboembolism

Hormone Therapy and Thromboembolism

Several investigations have found that a higher risk of thromboembolism is associated with hormone therapy. According to the WHI study, combined hormone therapy increased the risk of venous thrombosis and pulmonary embolism in 15 out of every 10,000 women. Women on an estrogen-only regimen had a higher risk of venous thrombosis, but their risk of pulmonary emboli was not statistically meaningful.

Thromboembolic consequences are more likely when there is an existing coagulopathy. Transdermal hormone therapy has been linked to a decreased risk of cancer.


Hormone Therapy and Biliary Diseases

Cholelithiasis is common in postmenopausal women, as becoming older and being overweight are both risk factors for the disease. This risk was found to be higher in postmenopausal women consuming hormone therapy in several trials, including the WHI. For women receiving estrogen-only formulations, the annual incidence of any gallbladder event was 79 events per 10,000 person-years, compared to 48 occurrences per 10,000 person-years for placebo. for example, combined estrogen and progestogen had 56 occurrences per 10,000 person-years compared to 3 events per 10,000 person-years for placebo.



When all possibilities are evaluated, any woman going through menopause should keep in mind what is in her greatest physical and emotional interests. While some women claim that using hormone replacement medications will permanently reduce their risks, others fear that the advantages will not be sufficient to balance the hazards. As a result, each woman has a responsibility to her own body's health. Which choice do you think is the greatest for you at that point in your life? If they prefer to try other options first and use hormone therapy only as a last option, that is their choice. It's not about making the final decision; it's about assisting these ladies in weighing the benefits and hazards of taking these treatments and allowing them to make an informed decision. Traditional medicine, in my opinion, should encourage drug knowledge in order to better enable people to manage their illness and practice individual preventive care. Natural medications on the market now appear to offer optimism for the future of alternative medicine in the field of menopause therapy, but more studies and research are required. As a result, menopause and associated symptoms will tend to be difficult for women to treat for some time.